沙格列汀和格列本脲对2型糖尿病大鼠主动脉内皮细胞核因子κB及血管细胞间黏附因子1表达的影响

The effect of saxagliptin versus glibenclamide on the expression of nuclear factorκB and vascular cell adhesion molecule 1 in aorta endothelium of type 2 diabetic rats

目的观察沙格列汀对T2DM大鼠主动脉内皮细胞核因子κB(NF-κB)、血管细胞间黏附因子1(VCAM-1)表达的影响。方法将成模大鼠分为糖尿病对照(DM)组、格列本脲治疗(DMG)组和沙格列汀治疗(DMS)组。DMG、DMS组分别予格列本脲、沙格列汀治疗8周。12周末检测各组FPG、FIns、血脂、NF-κB和VCAM-1表达,计算胰岛素抵抗指数(HOMA-IR),观察大鼠主动脉形态学变化。结果 12周末,与DMG组比较,DMS组FIns[(11.38±1.56)vs(6.13±0.54)μIU/ml]、TG[(1.17±0.15)vs(0.72±0.25)mmol/L]、LDL-C[(0.57±0.05)vs(6.13±0.54)mmol/L]、HOMA-IR[(12.78±1.53)vs(6.78±0.57)]、NF-κB平均灰度值[(143.33±13.38)vs(121.67±11.43)]和VCAM-1平均灰度值[(153.33±12.74)vs(133.00±11.53)]表达降低(P<0.05)。结论沙格列汀在改善糖、脂代谢的同时,可下调糖尿病大鼠主动脉内皮升高的NF-κB、VCAM-1蛋白表达量,可能参与改善大血管并发症。

Objective To investigate the effects of saxagliptin versus glibenclamide on the expression of nuclear factor κB （NF-κB） and vascular cell adhesion molecule 1 （VCAM-1） in aorta endothelium of T2DM rats and the possible mechanism.Methods SD rats were induced into the model of T2DM rats with the method introduced before.Normal SD rats were as NC.Then the diabetic group was treated with Saxagliptin （DMS） and Glibenclamide （DMG） while other diabetic rats were treated with physiological saline （DM） for eight weeks.After that,blood was taken from abdominal aorta for examining biochemical indexes including FPG,FIns,TG,TC,HDL-C and LDL-C.The thoracic aorta was isolated to observe the histological parameters by HE stain.The protein expression of NF-κB and VCAM-1 in aorta endothelium was observed with immunohistochemical method.Results At the end of twelfth week,as compared with DMG group,DMS group showed lower levels of FIns [（6.13±0.54）vs （11.38±1.56）μIU/ml],TG [（0.72±0.25）vs（1.17零0.15）mmol/L],LDL-C [（0.52±0.03）vs（0.57± 0.05）mrnol/L],HOMA-IR [（6.78±0.57）vs（12.78±1.53）],NF-κB [（121.67± 11.43）vs（143.33± 13.38）] and VCAM-1 [（133.00±11.53）vs（153.33± 12.74）] （all P＜0.05）.Conclusion Saxagliptin is superior to glibenclamide for decreasing the expression of NF-κB and VCAM-1 in aorta endothelium,improving glucolipid metabolism and perhaps decreasing vascular complications in T2DM rats.